Syphilitic infection in the rabbit mimmics human primary and in some cases human secondary infection. There is no animal system, however, that exhibits either tertiary or congenital syphilis. Thus, current knowledge about tertiary and congental syphilis is solely limited to clinical descriptions of human cases. The purpose of this proposed research is to use an interdisciplinary approach(anatomy, physiology, microbiology) to develop insight into the tissue pathology associated with these two syndromes. Two separate approaches will be used. First, in vitro experiments will be performed to assess pathologic damage in either isolated tissues or in cultured cells derived from isolated tissues. This research will attempt to define tissue damage either as a direct action of T. pallidum or as an indirect action due to the inflammation that accompanies the infection. The tissues to be investigated relate to those specifically implicated in tertiary and congenital syphilis: nerve, muscle, brain capillaries (neurosyphilis); aorta and heart (cardiovascular syphilis); and bone and cartilage. Attempts will be made to demonstrate significant histopathology in each tissue. Preliminary experiments have already demonstrated treponemal mediated in vitro damage to nerve, muscle, and capillaries. In addition, nerve impulse transmission and beating of heart cells are impaired by T. pallidum. The second approach involves in vivo experiments using rabbits. Attempts will be made to induce gumma formation and to develop a model for congenital syphilis by infecting pregnant rabbits. Subsequent birth defects will be evaluated in terms of specific treponemal damage.